Hematology Self-Renewal and Differentiation

Questions and Answers

What can result from a defect in the differentiation ability of cells?

Bone marrow diseases like anaemia (correct)

Leukaemia

Blood clots

Infection

Which transcription factor is involved in committing cells to the myeloid lineage?

CEBP

PU.1 (correct)

GATA2

GATA3

What is the role of transcription factors in HSCs?

They only promote cell death

They only assist in DNA replication

They regulate the self-renewal and differentiation capacity (correct)

They have no known function

Which factor is NOT associated with self-renewal potential in HSCs?

GATA1 Signup and view all the answers

How does epigenetics affect HSCs?

It controls gene activity without changing the DNA Signup and view all the answers

Which transcription factors are involved in the commitment to lymphoid lineage?

GATA3 and IKAROS Signup and view all the answers

What could increased self-renewal in HSCs lead to?

Leukaemia Signup and view all the answers

Which of the following statements about transcription factors is true?

Each factor is associated with a specific lineage commitment. Signup and view all the answers

What is the primary role of the INK4 family of proteins?

Repress the activity of cyclin-D_CDK4/6 complexes Signup and view all the answers

Which of the following is a characteristic of proto-oncogenes?

They can mutate to become oncogenes Signup and view all the answers

What is the function of the CIP/KIP family of proteins?

Suppress the cyclin-E_CDK2 complex Signup and view all the answers

Which statement accurately describes the relationship between proto-oncogenes and growth factors?

Proto-oncogenes promote cell cycle progression only when growth factors are available Signup and view all the answers

Which of the following roles does a tumour suppressor have?

Inhibit cellular proliferation Signup and view all the answers

How do oncogenes differ from proto-oncogenes?

Oncogenes are mutated forms that increase activity Signup and view all the answers

What factors, aside from cell cycle regulatory proteins, influence the fate of HSCs?

Transcription factors, growth factors, and signaling pathways Signup and view all the answers

What is the consequence of dysregulated cell cycle processes due to oncogenes?

Cellular transformation leading to cancer Signup and view all the answers

What is the effect of excessive ROS on hematopoietic stem cells (HSCs)?

It causes stem cell senescence or aging and cell death. Signup and view all the answers

How do the oxygen levels in the osteoblastic and vascular niches differ?

The vascular niche has a higher oxygen level compared to the osteoblastic niche. Signup and view all the answers

What role does oxidative stress play in cancer progression?

It enhances cellular proliferation and increases DNA damage. Signup and view all the answers

What is a characteristic of adult hematopoietic stem cells (HSCs) in terms of their energy source?

They reside in hypoxic niches and have a low metabolic rate. Signup and view all the answers

What is the potential role of the osteoblastic niche according to the dynamic model of hematopoiesis?

It serves as a reservoir for HSC storage. Signup and view all the answers

Which statement best describes the effect of mild ROS increase in HSCs?

It induces lineage differentiation. Signup and view all the answers

What distinguishes cancer stem cells from normal stem cells in terms of their niche interaction?

The signaling balance in cancer stem cells leans towards proliferation. Signup and view all the answers

What condition can occur in quiescent HSCs if oxidative stress is managed correctly?

Maintenance of low ROS levels. Signup and view all the answers

What role does SDF1 (CXCL12) play in relation to HSCs?

It promotes the self-renewal capacity of HSCs. Signup and view all the answers

Which cells are predominantly responsible for secreting CXCL12 in the bone marrow niches?

CXCL12 abundant reticular (CAR) cells Signup and view all the answers

Where do quiescent HSCs primarily localize within the bone marrow?

At the highest point of the hypoxic gradient Signup and view all the answers

What is the main energy source for quiescent HSCs residing in a hypoxic environment?

Glycolysis Signup and view all the answers

How does oxidative stress affect HSCs?

It leads to increased levels of ROS without control. Signup and view all the answers

What is a consequence of decreased CXCL12 expression in the bone marrow?

Enhanced migration of HSCs Signup and view all the answers

Which category of HSCs primarily relies on mitochondrial oxidative phosphorylation for energy?

Cycling HSCs Signup and view all the answers

What is the relationship between reactive oxygen species (ROS) and antioxidant enzymes in normal physiological conditions?

They maintain a balance under normal conditions. Signup and view all the answers

What is the defining characteristic of asymmetric division?

One daughter cell remains a stem cell while the other becomes a progenitor cell. Signup and view all the answers

Which phase of the cell cycle is characterized by DNA synthesis?

S phase Signup and view all the answers

Which cyclin is associated with the CDK4/6 complex for cell cycle entry?

Cyclin D Signup and view all the answers

What role do cyclin-dependent kinase inhibitors (CKIs) play in cell cycle regulation?

They maintain HSCs in a quiescent state. Signup and view all the answers

How do CDKs help HSCs transition into the G1 phase?

By forming complexes with their cyclin partners. Signup and view all the answers

What is the primary function of retinoblastoma (Rb) proteins in HSC regulation?

To repress entry into the cell cycle. Signup and view all the answers

Which CDK is not paired with its cyclin partner in the content provided?

CDK6 - Cyclin B Signup and view all the answers

Which function is least related to cyclin-dependent protein kinases (CDKs)?

Inhibiting the cell cycle progression. Signup and view all the answers

Study Notes

Self-Renewal and Differentiation Balance

Disruption in self-renewal and differentiation balance can lead to haematological diseases.
Defective differentiation causes blood cell shortages, leading to conditions like anemia.
Increased self-renewal can lead to leukemia.

Role of Transcription Factors

Transcription factors such as GATA2, BMI1, and GFI1 regulate self-renewal of hematopoietic stem cells (HSCs).
PU.1 and CEBP drive myeloid lineage commitment.
GATA2 and GATA1 promote differentiation into erythrocytes and megakaryocytes.
GATA3 and IKAROS facilitate lymphoid lineage commitment.

Epigenetic Modifications

Epigenetic modifications control gene activity without altering DNA sequence.
Symmetric differentiation results in two progenitor cells.
Asymmetric division produces one stem cell and one progenitor cell.

Cell Cycle Regulation of HSCs

HSCs undergo G0 phase (quiescence) before cycling through interphase (G1, S, G2) and mitosis.
Cyclin-dependent protein kinases (CDKs) regulate phases of the cell cycle via cyclin partners.
CDK4/6 and cyclin D form a complex to phosphorylate retinoblastoma proteins, activating E2f and facilitating G1 entry.

Cyclin-Dependent Kinase Inhibitors (CKIs)

CKIs (e.g., p15, p16, p21) prevent CDK activity to maintain HSC quiescence.
INK4 family inhibits cyclin-D_CDK4/6 complexes.
CIP/KIP family suppresses cyclin-E_CDK2 complex.

Regulation of HSC Fate

HSC fate is influenced by transcription factors, growth factors, and signaling pathways to maintain blood homeostasis.

Proto-Oncogenes vs Tumor Suppressors

Proto-oncogenes are positive regulators, enhancing cellular proliferation.
Tumor suppressors act as negative regulators, inhibiting proliferation.
Oncogenes arise from mutated proto-oncogenes, driving unchecked cell cycle progression.

Stem Cell Niches

HSCs are located in bone marrow niches, with quiescent HSCs found in hypoxic environments using anaerobic glycolysis for energy.
Cycling HSCs rely on aerobic respiration for energy.

Reactive Oxygen Species (ROS)

ROS generated during aerobic metabolism can affect HSC proliferation and aging.
Excessive ROS creates oxidative stress, leading to differentiation issues and potential cell death.

Dynamic HSC Migration

HSCs migrate between osteoblastic and vascular niches depending on environmental conditions.
Osteoblastic niche serves as a reservoir; vascular niche supports proliferation and differentiation.

Cancer Stem Cell Niche

Cancer stem cells emerge from mutations, becoming highly proliferative.
Signaling balance within the niche is altered in cancer stem cells, favoring proliferation over normal stem cell regulation.

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Description

Explore the critical balance between self-renewal and differentiation in hematopoiesis. This quiz addresses how disruptions in this balance can lead to diseases such as anemia and leukemia, and the role of transcription factors in regulating these processes.